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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Journal of Hematology & Oncology 1/2014

Intratumoral anti-HuD immunotoxin therapy for small cell lung cancer and neuroblastoma

Zeitschrift:
Journal of Hematology & Oncology > Ausgabe 1/2014
Autoren:
Debra Ehrlich, Bo Wang, Wei Lu, Peter Dowling, Ruirong Yuan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13045-014-0091-3) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

DE performed animal experiments, performed data analysis, and prepared and revised the manuscript. BW performed in vitro experiments, animal experiments on the nude mouse model, prepared the manuscript, analysed data, and prepared figures. LW performed data analysis and manuscript revision. PD revised the manuscript and aided in study design. RY designed and supervised the study, prepared the manuscript, analysed data, and performed final revisions. All authors agree with the contents of this submission along with its accuracy and integrity. All authors read and approved the final manuscript.

Abstract

Background

Most patients with small cell lung cancer (SCLC) or neuroblastoma (NB) already show clinically detectable metastases at diagnosis and have an extremely poor prognosis even when treated with combined modalities. The HuD-antigen is a neuronal RNA-binding protein that is expressed in 100% of SCLC tumor cells and over 50% of neuroblastoma cells. The correlation between high titers of circulating anti-HuD antibodies in patients and spontaneous tumor remission suggests that the HuD-antigen might be a potential molecular target for immunotherapy.

Methods

We have constructed a new antibody-toxin compound (called BW-2) by assembling a mouse anti-human-HuD monoclonal antibody onto streptavidin/saporin complexes.

Results

We found that the immunotoxin BW-2 specifically killed HuD-positive human SCLC and NB cancer cells at very low concentrations in vitro. Moreover, intratumoral immunotoxin therapy in a nude mouse model of human SCLC (n = 6) significantly reduced local tumor progression without causing toxicity. When the same intratumoral immunotoxin protocol was applied to an immunocompetent A/J mouse model of NB, significant inhibition of local tumor growth was also observed. In neuroblastoma allografted A/J mice (n = 5) treated twice with intratumoral immunotoxin, significant tumor regression occurred in over 80% of the animals and their duration of tumor response was significantly prolonged.

Conclusions

Our study suggests that anti-HuD based immunotoxin therapy may prove to be an effective alternative treatment for patients with SCLC and NB.

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Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Authors’ original file for figure 4
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Authors’ original file for figure 5
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Literatur
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